Twelve patients (pts) with advanced stages of malignancies received 75 g m squared/day of Thymidine (TdR) given as a continuous infusion IV for 5 days. Hematologic toxicity was as follows: leukopenia (57 percent), thrombocytopenia (29 percent), and anemia (52 percent). Non-hematologic toxicities were gastrointestinal (nausea, vomiting and anorexia 91 percent, diarrhea 73 percent, and indigestion 22 percent) and central nervous system (somnolence 82 percent, severe headaches 73 percent, visual illusions 56 percent, and memory impariment 22 percent). Alopecia occurred in pts who had received more than 5 courses. No renal or hepatic toxicity or allergic manifestations were observed. Thymine crystals were noted in the pts' urine after refrigeration. Tumor regression (less than PR) occurred in 1 pt with melanoma; 3 out of 4 pts with acute leukemia had decrease in peripheral WBC counts and blasts but no bone marrow response; 1 pt with ANLL also had shrinkage of hepatosplenomegaly; 3 pts with colon cancer and 1 with unknown primary had stable disease. Pharmacokinetic studies have shown that millimolar concentrations of TdR and thymine were reached within 12 hours and maintained during the entire period of treatment. The plasma half-life of TdR was approximately 100 minutes. Forty to 67 percent TdR and 13-18 percent thymine were excreted in the urine. One-third of the plasma TdR concentration was measurable in the cerebrospinal fluid. Further trials to evaluate the efficacy of TdR are ongoing.